Pembrolizumab and Magnetic Resonance Imaging With Ferumoxytol in Treating Patients With Non-small Cell Lung Cancer and Brain Metastases

Inclusion Criteria:

• Be willing and able to provide written informed consent/assent for the trial
• Have a histologically confirmed diagnosis of NSCLC
• Have up to ten measurable (by Response Assessment in Neuro-Oncology Criteria [RANO])brain metastasis planned for stereotactic radiosurgery
• Have PD-L1 expression of greater than 1%
• Subjects may already be receiving PD-(L)1 (including pembrolizumab or other PD-[L]1inhibitors such as nivolumab, atezolizumab, avelumab, durvalumab) for the treatment ofsystemic disease; a washout period of at least 3 weeks is required from the last doseof PD-(L)1 inhibitor
• Subjects with EGFR or ALK genomic tumor aberrations should have documented diseaseprogression on Food and Drug Administration (FDA)-approved therapy for theseaberrations; subjects with EGFR or ALK genomic tumor aberrations who develop new brainmetastases may be included at the discretion of the treating physician
• Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG)performance scale
• Absolute neutrophil count (ANC) >= 1,500 /mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO)dependency (within 7 days of assessment)
• Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculatedcreatinine clearance (glomerular filtration rate [GFR] can also be used in place ofcreatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatininelevels > 1.5 X institutional ULN
• Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with totalbilirubin levels > 1.5 ULN
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) andalanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 XULN OR =< 5 X ULN for subjects with liver metastases
• Albumin >= 2.5 mg/dL
• International normalized ratio (INR) or prothrombin rime (PT) =< 1.5 X ULN unlesssubject is receiving anticoagulant therapy as long as PT or partial thromboplastintime (PTT) is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receivinganticoagulant therapy as long as PT or PTT is within therapeutic range of intended useof anticoagulants
• Female subject of childbearing potential should have a negative urine or serumpregnancy within 72 hours prior to receiving the first dose of study medication; ifthe urine test is positive or cannot be confirmed as negative, a serum pregnancy testwill be required
• Female subjects of childbearing potential should be willing to use 2 methods of birthcontrol or be surgically sterile, or abstain from heterosexual activity for the courseof the study through 120 days after the last dose of study medication; subjects ofchildbearing potential are those who have not been surgically sterilized or have notbeen free from menses for > 1 year; male subjects should agree to use an adequatemethod of contraception starting with the first dose of study therapy through 120 daysafter the last dose of study therapy

Exclusion Criteria:

• Has evidence of leptomeningeal disease on MRI or in cerebrospinal fluid (CSF)
• If tumor demonstrates EGFR or ALK genomic tumor aberrations, subject should havedocumented disease progression on FDA-approved therapy for these aberrations
• Has a diagnosis of immunodeficiency and is not on continuous daily immunosuppressivetherapy within 7 days prior to the first dose of trial treatment; (subjects mayreceive steroids before or after SRS to prevent or manage cerebral edema; inhalationalsteroids are permitted)
• Has previously progressed on a PD-1 or PD-L1 checkpoint inhibitor for systemic disease
• Has a known history of active TB (Bacillus tuberculosis)
• Has hypersensitivity to pembrolizumab, gadolinium, or ferumoxytol or any of theirexcipients
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to studyday 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse eventsdue to agents administered more than 4 weeks earlier
• Note: The use of denosumab is an exception to this criterion
• Subject who has not recovered (i.e., =< grade 1 or at baseline) from adverse eventsdue to a previously administered agent
• Note: Subjects with =< grade 2 neuropathy are an exception to this criterion andmay qualify for the study
• Note: Subjects with =< grade 2 hematologic toxicities are an exception to thiscriterion and may qualify for the study
• Note: Subjects with =< grade 2 fatigue are an exception to this criterion and mayqualify for the study
• Has a known additional malignancy that is progressing or requires active treatment;exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of theskin that has undergone potentially curative therapy or in situ cervical cancer
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressivedrugs); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroidreplacement therapy for adrenal or pituitary insufficiency, etc.) is not considered aform of systemic treatment
• Has known history of, or any evidence of active, non-infectious pneumonitis
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormalitythat might confound the results of the trial, interfere with the subject'sparticipation for the full duration of the trial, or is not in the best interest ofthe subject to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere withcooperation with the requirements of the trial
• Is pregnant or breastfeeding, or expecting to conceive or father children within theprojected duration of the trial, starting with the pre-screening or screening visitthrough 120 days after the last dose of trial treatment
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) orhepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] isdetected)
• Has received a live vaccine within 30 days of planned start of study therapy
• Note: Seasonal influenza vaccines for injection are generally inactivated fluvaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist)are live attenuated vaccines, and are not allowed
• Subjects with clinically significant signs of uncal herniation, such as acutepupillary enlargement, rapidly developing motor changes (over hours), or rapidlydecreasing level of consciousness, are not eligible
• Subjects with known allergic or hypersensitivity reactions to parenteral iron,parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharidepreparations; subjects with significant drug or other allergies or autoimmune diseasesmay be enrolled at the investigator's discretion
• Subjects who have a contraindication for 3 tesla (3T) MRI: metal in their bodies (acardiac pacemaker or other incompatible device), are severely agitated, or have anallergy to gadolinium containing contrast material
• Subjects with known iron overload (genetic hemochromatosis); in subjects with a familyhistory of hemochromatosis, hemochromatosis must be ruled out prior to study entrywith normal values of the following blood tests: transferrin saturation (TS) test andserum ferritin (SF) test; all associated costs will be paid by the study
• Subject who have received ferumoxytol within 3 weeks of study entry
• Subjects with three or more drug allergies from separate drug classes